Modic changes in patients with lumbar disc herniation followed more than 1 year after lumbar discectomy: a systematic review and meta-analysis

Background Modic changes (MCs) are identified as an independent risk factor for low back pain. Different subtypes of MCs vary in their impact on postoperative pain relief. However, consensus on the transformation of postoperative MC fractions in patients with distinct MC subtypes is lacking. Methods This comprehensive systematic review and meta-analysis searched English-language articles in PubMed, Cochrane Library, Web of Science, and Embase databases until January 2024. Studies included focused on patients transitioning between various microcrack subtypes post-discectomy. The primary outcome measure was the transformation between different postoperative microcrack fractions. Results Eight studies with 689 participants were analyzed. Overall, there is moderate to high-quality evidence indicating differences in the incidence of MC conversion across MC subtypes. The overall incidence of MC conversion was 27.7%, with rates of 37.0%, 20.5%, and 19.1% for MC0, MC1, and MC2 subtypes, respectively. Thus, postoperative MC type transformation, particularly from preoperative MC0 to MC1 (17.7%) or MC2 (13.1%), was more common, with MC1 transformation being predominant. Patients with preoperative comorbid MC1 types (19.0%) exhibited more postoperative transitions than those with MC2 types (12.4%). Conclusion This study underscores the significance of analyzing post-discectomy MCs in patients with lumbar disc herniation, revealing a higher incidence of MCs post-lumbar discectomy, particularly from preoperative absence of MC to MC1 or MC2. Preoperative MC0 types were more likely to undergo postoperative MC transformation than combined MC1 or MC2 types. These findings are crucial for enhancing surgical outcomes and postoperative care.

Until the 2010s, follow-up studies of patients with MCs primarily focused on observing the natural progression of these changes, with limited emphasis on evaluating the impact of surgical interventions (Albert & Manniche, 2007;Jensen et al., 2009;Kuisma et al., 2006).Discectomy, a common medical procedure for severe disc herniation, has shown efficacy in patients who do not respond to long-term conservative treatment (Cenic & Kachur, 2009), especially in terms of reducing or eliminating low back pain in patients with various MC types (Nian et al., 2023).However, some articles have reported surgical promotion of Modic type transformation.For instance, Albert & Manniche (2007) noted a higher incidence of MCs among patients with low back pain who had undergone surgery within 1 year of follow-up than among those who did not undergo surgery.A systematic evaluation with higher-level evidence has shown that patients with preoperative MC1 tend to have poorer functional outcomes after discectomy, and MC after lumbar discectomy can significantly affect prognosis (Nian et al., 2023).While some studies have suggested a trend towards the conversion of MC0 and MC1 to MC2 (Albert & Manniche, 2007;Kuisma et al., 2006), a prospective cohort study pointed out a more complex pattern of MC transformation after limited discectomy in the lumbar spine (Bostelmann et al., 2019).
Therefore, understanding the impact of the type of MC alteration on pain and functional prognosis after discectomy is crucial.However, there is still a lack of high-level evidence regarding the postoperative transformation of MC alterations.This study aims to investigate the incidence and trend of MC transformation post-lumbar discectomy.

Study design
This review adhered to the MOOSE (Meta-analysis Of Observational Studies in Epidemiology) guidelines (Stroup et al., 2000) and was registered on PROSPERO (CRD42023465280), with an application submitted on September 29, 2023.Following registration, we initiated an initial search and pilot study selection process, followed by data extraction and analysis.

Search strategy
A comprehensive literature search was conducted across four databases: PubMed, Web of Science, Embase, and Cochrane up to January 2024.We used combinations of keywords such as "diskectomy or discectomy," "Modic changes or VESC," "Low back pain or LBP," and "Lumbar disc herniation" in the fields "abstract" and "title."The complete search strategy is detailed in Supplemental 1.Only published articles and human studies were included, with manual checks of references to maximize the number of documents cited.

Study selection
Inclusion criteria comprised studies where discectomy or microdiscectomy was performed for patients with lumbar disc herniation (LDH) combined with various Modic types.Additionally, studies needed to identify the type of MCs both preoperatively and postoperatively, including MC1 and MC2.Outcome indicators included preoperative and postoperative MC types.Both randomized controlled trials (RCTs) and non-RCTs studies were eligible, provided they were published in English.Exclusion criteria encompassed studies observing the natural evolution of MCs, those involving surgical procedures other than discectomy, those reporting incomplete follow-up data, and articles with non-extractable data such as case reports, reviews, or letters.

Data extraction
Two researchers independently reviewed and extracted data from included articles, including published authors, study year, type, duration, patient demographics, Modic type, surgical method, and outcome metrics at final follow-up.Disagreements were resolved through discussion.Data were formatted according to the Cochrane Handbook of Systematic Reviews (Higgins et al., 2019).

Risk of bias assessment
Two investigators evaluated all included studies.The quality of observational studies was assessed using the Newcastle-Ottawa Scale (NOS) (Bostelmann et al., 2019;Kawaguchi et al., 2023;Ohtori et al., 2010;Rahme et al., 2010;Takahashi et al., 2021;Yaman et al., 2017).The NOS scale (total score, 8), commonly employed as an evaluation tool for cohort studies, is composed of three parts: Selection of the study population, comparability between groups, and outcome measures.In the study population selection, one point was rated for meeting the representativeness of the exposed group, the method of selecting the nonexposed group, the method of determining exposure factors, and the determination of outcome indicators at the beginning of the study; two points for controlling for confounding factors during design and statistical analysis; and one point each for adequacy of the assessment of study outcomes, follow-up time, and follow-up in the outcome measures section.Table 1 presents detailed components of the NOS scale.Figure 1 illustrates the Risk of Bias (RoB2) tool used for the risk of bias evaluation for RCTs (el Barzouhi et al., 2014;Lee & Bae, 2015).Risk of bias may arise from various factors, including the country of study, selection of the study population, choice of procedures, and  duration of follow-up.Disagreements, if any, were resolved through consultation with an independent third party.

Data analysis
Post-surgery, MC types were categorized into MC0, MC1, and MC2 subtypes, and their conversion rates between groups were measured.Specific conversions (MC0→MC1, MC2 and MC3; MC1→MC0, MC2 and MC3; MC2→MC0, MC1 and MC3) between MC types were analyzed, including extreme values, which implies that both scenarios involving a complete set of conversions during measurements and those without any conversions are encompassed.The above steps are performed using the "metaprop" command in the Stata 17Ò software with associated meta-analysis plug-ins.Preoperative MC3 and mixed MC types were excluded due to sample size limitations and incomplete data.This study aimed to analyze MC conversion rates between different MC types as outcome metrics.We used preoperative and postoperative MCs as indicators, setting a 95% confidence interval (95% CI).Additionally, we conducted a meta-analysis of preoperative and postoperative MCs to compare the proportion of MC conversions across MC0, MC1, and MC2 groups.Meta-analysis was performed using a random-effects model based on data heterogeneity (I 2 > 50%).

Study selection
Initially, we identified 100 articles, which included 13 articles from PubMed, 18 articles from Embase, 63 articles from Web of Science, four articles from Cochrane, and two articles from manual search.After removing duplicates, 58 articles remained.Through title and abstract screening, 39 articles were further excluded, leaving 19 articles for full-text assessment.Subsequently, six studies were excluded due to no Modic type illustration, four for incomplete outcomes, and one for no clear surgical procedure, resulting in eight articles (Bostelmann et al., 2019;el Barzouhi et al., 2014;Kawaguchi et al., 2023;Lee & Bae, 2015;Mostofi, Moghaddam & Peyravi, 2018;Ohtori et al., 2010;Rahme et al., 2010;Takahashi et al., 2021;Yaman et al., 2017) included in the meta-analysis (Fig. 2).

Risk of bias assessments
All eight studies underwent NOS or RoB2 evaluation, with none deemed to be at high risk of bias.The scores varied, with three studies rated eight points, two studies rated eight points, one study rated seven points, and one study rated six points.After completing the methodology quality assessment, the results showed acceptable quality.Preoperative MCs Data extraction from all eight studies allowed for the analysis of MC conversion incidence between MC0, MC1, and MC2 groups.

DISCUSSION
To the best of our knowledge, this review presents the first examination of long-term outcomes (more than 1-year post-surgery) regarding MC transformations in patients with LDH, particularly those with a mix of preoperative MC types.The evidence, of moderate to high quality, indicates a higher likelihood of Modic type transitions in patients initially without preoperative MC (MC0) than in those with pre-existing combined MC types (MC+).Specifically, a significant proportion of patients transitioned to MC1 (17.7%), followed by MC2 (19.0%), while transitions to MC3 were notably infrequent (0%).Interestingly, individuals with a preoperative blend of MC1 types were more prone to such transformations than those with MC2 phenotypes, although the prevalence were similar (MC1 = 20.5%,MC2 = 19.1%).However, neither group showed evidence of reverting back to MC0.The process illustrating the conversion of Modic changes is depicted in Fig. 8. Previous research indicates that patients with LDH exhibiting combined preoperative MC1 are associated with diminished functional status post-discectomy.Traditionally, prognostic assessments post-discectomy have focused on preoperative MCs (Karadağ et al., 2022;Li et al., 2021;Ulrich et al., 2020;Xu et al., 2019), yet the impact of surgical intervention on MC trajectory has not been thoroughly examined.The transformation of MCs following surgery may significantly contribute to persistent postoperative pain, underscoring the importance of analyzing the prevalence and patterns of MCs post-lumbar discectomy for understanding surgical outcomes and refining clinical management strategies.Furthermore, the progression of Modic changes post-discectomy is clinically significant as it can influence long-term outcomes and pain management strategies in patients with lumbar disc herniation (Albert & Manniche, 2007;Jensen et al., 2012;Kuisma et al., 2007).A comprehensive understanding of these changes can aid in tailoring postoperative care and potentially enhancing patient prognosis.In our aggregate analysis, the preoperative incidences of MC0, MC1, and MC2 were found to be 37.0%, 20.5%, and 19.1%, respectively.Importantly, our study's MC prevalence substantially exceeded the rates observed in the general Danish population's natural progression (Jensen et al., 2009).This disparity may be attributed to the strong association between disc degeneration and MCs.Evidence from various studies supports a positive association between the emergence of MCs and progression of lumbar disc degeneration (Kjaer et al., 2005), with severe lumbar disc degeneration being more prevalent in patients exhibiting MCs (Özcan-Ekşi et al., 2021).
Recent scholarly efforts advocate for a nuanced classification of MCs, such as Xu et al. ( 2016)'s observation of mixed types combining endplate edema and sclerosis in MC patients.However, our study focused on traditional MC typology due to limited representation of mixed-type cases, potentially increasing heterogeneity and confounding factors in our findings.It is widely accepted that MCs can evolve from one type to another, representing different phases of the same pathological process.The concept of mixed types likely represents a transitional phase (Weishaupt et al., 1998), with evidence suggesting surgical interventions may accelerate this transition (Albert et al., 2008;Kanna et al., 2017), contrasting with the average follow-up duration in our included studies.Moreover, Bostelmann et al.'s (2019) study, which met our study's inclusion criteria, examined a population with low back pain persisting for just over 6 weeks, notably shorter than that in all included studies.This brief duration may indicate a higher prevalence of unstable MC1 in patients, potentially leading to more frequent MC transitions postsurgery.In eight studies, patients who underwent lumbar discectomy exhibited conversions between MC1 and MC2, with a higher incidence of transitioning from MC1 to MC2 preoperatively than from MC2 to MC1.Notably, no conversion to the more stable MC3 type was observed post-surgery, possibly due to the brief follow-up timeframe, highlighting the need for extended follow-up in future research.

Strengths and limitations
We conducted a comprehensive literature review and screening process spanning from 1998 to 2024, adhering to stringent MOOSE guidelines (Stroup et al., 2000).Our synthesized findings, supported by postoperative follow-up data, provide a robust foundation for evaluating the implications of MCs in postoperative scenarios.However, the study is not without limitations.First, the number of relevant articles included was limited, potentially resulting in a significant deviation from the actual MC conversion rate.Second, this study specifically focuses on patients who are more than 1 year post-surgery; therefore, changes that occur within 1 year after surgery remain unknown.Third, the dynamic nature of MC conversion, combined with varying follow-up durations postdiscectomy, complicated our understanding of the frequency and timing of such transformations.Fourth, variations in MC types at different follow-up intervals remain unclear.Finally, the scarcity of data in the selected literature limits our insight into the precise locations of MCs and their postoperative implications on adjacent spinal segments.

CONCLUSION
Our findings suggest an increased likelihood of postoperative MC transformation, particularly from no preoperative MC (MC0) to MC1 or MC2, with a higher prevalence of MC1.Notably, patients exhibiting a combination of preoperative MC1 types experienced more frequent postoperative transformations than those with MC2 types.This study elucidates the characteristic changes in Modic change (MC) types observed among patients undergoing lumbar discectomy, thereby enhancing comprehension of surgical outcomes and facilitating improvements in postoperative clinical care quality.

Figure 1
Figure 1 The RoB2 tool utilized for risk of bias assessment of two RCT articles.Each point illustrates the average performance of all included articles on the risk of bias corresponding to each section.Green indicates the low risk meanwhile the yellow indicates the unclear risk.Full-size  DOI: 10.7717/peerj.17851/fig-1

Table 1
The detailed description of newcastle-ottawa scale (NOS) used to evaluate included non-RCT articles.Representativeness of the exposed cohort; B, Selection of the non-exposed cohort; C, Ascertainment of exposure; D, Demonstration that outcome of interest was not present at start of study; E, Comparability of cohorts on the basis of the design or analysis; F, Assessment of outcome; G, Follow-up long enough for outcomes to occur; H, Adequacy of follow up of cohort.

Table 2
(Lee & Bae, 2015) characteristics of the included studies, including country of origin, patient demographics, procedure types, body mass index, duration of pain, MC groups, follow-up time, and MC diagnosis criteria.All studies utilized similar MC diagnosis criteria and grouping standards.Although some articles mentioned inclusion criteria for MC3 and mixed MC types(Lee & Bae, 2015), these subtypes were excluded due to limited data.All eight studies presented outcome indicators at both preoperative and postoperative time points.In total, 728 patients diagnosed with LDH were identified, with 689 patients meeting the inclusion criteria (445 with MC0 (64.6%), 70 with MC1 (10.2%), and 174 with MC2 (25.2%)), after excluding cases with preoperative MC3, mixed MC types, or lost follow-up.The incidence of MC conversion in all groups was 27.7%.Patients with MC0 exhibited a higher incidence of conversion to any other MC types (37.0%), compared to those withMC1 and MC2 (20.5% and 19.1%, respectively;.

Table 2
Summary of eight included articles.